Clocking in to immunity

Nature reviews. Immunology, Journal Year: 2018, Volume and Issue: 18(7), P. 423 - 437

Published: April 16, 2018

Language: Английский

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Genomics of circadian rhythms in health and disease

Genome Medicine, Journal Year: 2019, Volume and Issue: 11(1)

Published: Dec. 1, 2019

Abstract Circadian clocks are endogenous oscillators that control 24-h physiological and behavioral processes. The central circadian clock exerts over myriad aspects of mammalian physiology, including the regulation sleep, metabolism, immune system. Here, we review advances in understanding genetic sleep through system, as well impact dysregulated gene expression on metabolic function. We also recent studies have begun to unravel clock’s role controlling cardiovascular nervous systems, gut microbiota, cancer, aging. Such these systems relies, part, transcriptional regulation, with evidence for genome-wide chromosome organization. These novel insights into genomic human physiology provide opportunities discovery improved treatment strategies new biological underpinnings disease.

Language: Английский

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Circadian disruption and human health

Journal of Clinical Investigation, Journal Year: 2021, Volume and Issue: 131(19)

Published: Sept. 30, 2021

Circadian disruption is pervasive and can occur at multiple organizational levels, contributing to poor health outcomes individual population levels. Evidence points a bidirectional relationship, in that circadian increases disease severity many diseases disrupt rhythms. Importantly, increase the risk for expression development of neurologic, psychiatric, cardiometabolic, immune disorders. Thus, harnessing rich findings from preclinical translational research biology enhance via circadian-based approaches represents unique opportunity personalized/precision medicine overall societal well-being. In this Review, we discuss implications human using bench-to-bedside approach. science applied clinical population-based Given broad regulation health, Review focuses its discussion on selected examples metabolic, cardiovascular, allergic, immunologic disorders highlight interrelatedness between potential interventions, such as bright light therapy exogenous melatonin, well chronotherapy improve and/or modify outcomes.

Language: Английский

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Perfect timing: circadian rhythms, sleep, and immunity — an NIH workshop summary

JCI Insight, Journal Year: 2020, Volume and Issue: 5(1)

Published: Jan. 15, 2020

Recent discoveries demonstrate a critical role for circadian rhythms and sleep in immune system homeostasis. Both innate adaptive responses — ranging from leukocyte mobilization, trafficking, chemotaxis to cytokine release T cell differentiation —are mediated time of day–dependent manner. The National Institutes Health (NIH) recently sponsored an interdisciplinary workshop, “Sleep Insufficiency, Circadian Misalignment, the Immune Response,” highlight new research linking biology function identify areas high translational potential. This Review summarizes topics discussed highlights immediate opportunities delineating clinically relevant connections among biological rhythms, sleep, regulation.

Language: Английский

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Circadian rhythms in the absence of the clock gene Bmal1

Science, Journal Year: 2020, Volume and Issue: 367(6479), P. 800 - 806

Published: Feb. 14, 2020

Circadian (~24 hour) clocks have a fundamental role in regulating daily physiology. The transcription factor BMAL1 is principal driver of molecular clock mammals. Bmal1 deletion abolishes 24-hour activity patterning, one measure output. We determined whether function necessary for oscillations skin fibroblasts and liver slices. Unexpectedly, knockout mice, both tissues exhibited the transcriptome, proteome, phosphoproteome over 2 to 3 days absence any exogenous drivers such as light or temperature cycles. This demonstrates competent pacemaker knockouts. suggest that might be underpinned by transcriptional regulation recruitment ETS family factors, nontranscriptionally co-opting redox oscillations.

Language: Английский

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Melatonin: Roles in influenza, Covid‐19, and other viral infections

Reviews in Medical Virology, Journal Year: 2020, Volume and Issue: 30(3)

Published: April 21, 2020

Summary There is a growing appreciation that the regulation of melatonergic pathways, both pineal and systemic, may be an important aspect in how viruses drive cellular changes underpin their control function. We review pathway role viral infections, emphasizing influenza covid‐19 infections. Viral, or preexistent, suppression melatonin disinhibits neutrophil attraction, thereby contributing to initial “cytokine storm”, as well other immune cells. Melatonin induces circadian gene, Bmal1, which pyruvate dehydrogenase complex (PDC), countering inhibition Bmal1/PDC. PDC drives mitochondrial conversion acetyl‐coenzyme A (acetyl‐CoA), increasing tricarboxylic acid cycle, oxidative phosphorylation, ATP production. Pineal attenuates this, preventing “resetting” metabolism. This especially relevant cells, where shifting metabolism from glycolytic switches cells reactive quiescent phenotypes. Acetyl‐CoA necessary cosubstrate for arylalkylamine N‐acetyltransferase, providing acetyl group serotonin, initiating pathway. Consequently, regulates cell phenotype. Virus‐ cytokine‐storm‐driven therefore responses. Virus‐and cytokine storm‐driven also increase gut permeability dysbiosis, suppressing levels short‐chain fatty acid, butyrate, circulating lipopolysaccharide (LPS). The alterations butyrate LPS can promote replication host symptom severity via impacts on Focussing regulators has treatment implications

Language: Английский

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The circadian immune system

Science Immunology, Journal Year: 2022, Volume and Issue: 7(72)

Published: June 3, 2022

The immune system is highly time-of-day dependent. Pioneering studies in the 1960s were first to identify responses be under a circadian control. Only last decade, however, have molecular factors governing rhythms been identified. These revealed complex picture of interconnectivity rhythmicity within cells with that their environment. Here, we provide global overview system, focusing on recent advances rapidly expanding field immunology.

Language: Английский

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Basic helix–loop–helix ARNT like 1 regulates the function of immune cells and participates in the development of immune-related diseases

Burns & Trauma, Journal Year: 2025, Volume and Issue: 13

Published: Jan. 1, 2025

The circadian clock is an internal timekeeper system that regulates biological processes through a central and peripheral clocks controlling various genes. Basic helix-loop-helix ARNT-like 1 (BMAL1), also known as aryl hydrocarbon receptor nuclear translocator-like protein (ARNTL1), key component of the clock. deletion BMAL1 alone can abolish rhythms human body. plays critical role in immune cell function. Dysregulation linked to immune-related diseases such autoimmune diseases, infectious cancer, vice versa. This review highlights significant governing cells, including their development, differentiation, migration, homing, metabolism, effector functions. study explores how dysregulation have far-reaching implications potentially contribute onset sepsis, trauma. Furthermore, this discusses treatments for target disorders. Understanding impact on function provide insights into pathogenesis help development more effective treatment strategies. Targeting has been demonstrated achieve good efficacy indicating its promising potential targetable therapeutic these diseases.

Language: Английский

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Mood, the Circadian System, and Melanopsin Retinal Ganglion Cells

Annual Review of Neuroscience, Journal Year: 2017, Volume and Issue: 40(1), P. 539 - 556

Published: May 19, 2017

The discovery of a third type photoreceptors in the mammalian retina, intrinsically photosensitive retinal ganglion cells (ipRGCs), has had revolutionary impact on chronobiology. We can now properly account for numerous non-vision-related functions light, including its effect circadian system. Here, we give an overview ipRGCs and their function as it relates specifically to mood biological rhythms. Although disruptions have been traditionally hypothesized be mediators light's effects mood, here present alternative model that dispenses with assumptions causality between two phenomena explains regulation by light via another ipRGC-dependent mechanism.

Language: Английский

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BMAL1 links the circadian clock to viral airway pathology and asthma phenotypes

Mucosal Immunology, Journal Year: 2017, Volume and Issue: 11(1), P. 97 - 111

Published: April 12, 2017

Patients with asthma experience circadian variations in their symptoms. However it remains unclear how specific aspects of this common airway disease relate to clock genes, which are critical the generation rhythms mammals. Here, we used a viral model acute and chronic examine disruption affects asthmatic lung phenotypes. Deletion core gene bmal1 or environmental function by jet lag exacerbated bronchiolitis caused Sendai virus (SeV) influenza A mice. Post-natal deletion was sufficient trigger increased SeV susceptibility correlated impaired control replication. Importantly, bmal1-/- mice developed much more extensive asthma-like changes post infection, including mucus production resistance. In human samples from two cohorts, observed altered expression patterns multiple genes. Our results suggest role for development via regulation antiviral responses triggers asthma.

Language: Английский

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